Cyclosporine (CyA; formerly called cyclosporin A) is a cyclic peptide produced by the fungus Tolypocladium inflatum. CyA is an immunosupressant administered to human alloqeneic transplant recipients or human subjects undergoing treatment for an autoimmune disease such as myasthenia gravis. A problem with CyA, however, is its organ toxicity. The major toxic side-effect of CyA is nephrotoxicity, but hepatotoxicity and cardiotoxicity have also been noted.
U.S. Pat. No. 4,306,075 describes novel benzindene prostaglandins which produce various pharmacological responses, such as inhibition of platelet aggregation, reduction of gastric secretion, and bronchodilation. It is indicated that the compounds have useful application as anti-thrombotic agents, anti-ulcer agents, and anti-asthma agents. There is no indication that these compounds may be used to combat tissue transplant rejection.
European Patent Application 347243 of A.S. Tadepalli et al. discloses fused-ring prostaglandin derivatives for treating or preventing pulmonary hypertension and for diagnosing primary pulmonary hypertension patients who have active pulmonary vasoconstriction (see also U.S. Pat. No. 5,028,628).
The present invention is based on our ongoing research into cyclosporine therapies.